Geschmack ist vorhersagbar: Mit FlavorMiner. FlavorMiner heißt das Tool, das IPB-Chemiker und Partner aus Kolumbien jüngst entwickelt haben. Das Programm kann, basierend auf maschinellem Lernen (KI), anhand der…
Seit Februar 2021 bietet Wolfgang Brandt, ehemaliger Leiter der Arbeitsgruppe Computerchemie am IPB, sein Citizen Science-Projekt zur Pilzbestimmung an. Dafür hat er in regelmäßigen Abständen öffentliche Vorträge zur Vielfalt…
Smolková, R.; Smolko, L.; Samoľová, E.; Morgan, I.; Rennert, R.; Kaluđerović, G. N.;Novel Zn(ii), Co(ii) and Cu(ii) diflunisalato complexes with neocuproine and their exceptional antiproliferative activity against cancer cell linesDalton Trans.5317595-17607(2024)DOI: 10.1039/d4dt01736f
Three novel complexes of deprotonated diflunisal (dif) with neocuproine (neo) were synthesized and characterized via elemental, spectral (UV-vis, FTIR, fluorescence, and mass spectrometry), and single-crystal X-ray diffraction analyses. Although the compounds shared a similar composition of [MCl(dif)(neo)], where M represents Zn(II) (1), Co(II) (2) and Cu(II) (3), only 1 and 2 were isostructural, while 3 differed in both the molecular and supramolecular structures. In all three complex molecules, the central atom is coordinated by two nitrogen atoms of neo in a bidentate chelate mode, and one chlorido ligand and dif is bonded in either a monodentate mode via one oxygen atom of the carboxylate in 1 and 2 or in a bidentate chelate mode via both carboxylate oxygen atoms in 3. All three compounds demonstrated remarkable antiproliferative activity against human prostate (PC-3), colon (HCT116) and breast (MDA-MB-468) cancer cell lines with IC50 values in the nanomolar range, with the lowest values observed in the case of PC-3 and MDA-MB-468 with 2 (20.0 nM) and 3 (31.1 nM), respectively. Moreover, complex 2, as the most active, was further investigated for its potential to induce perturbations in the cell cycle of PC-3 cells. The results indicated an induction of caspase-independent apoptosis. The interaction of the complexes with genomic DNA isolated from the respective cancer cell lines was evaluated for the intercalative mode, with binding strength correlated with the antiproliferative activity against PC-3 and MDA-MB-468 cancer cell lines.
Publikation
Predarska, I.; Saoud, M.; Morgan, I.; Eichhorn, T.; Kaluđerović, G. N.; Hey-Hawkins, E.;Cisplatin−cyclooxygenase inhibitor conjugates, free and immobilised in mesoporous silica SBA-15, prove highly potent against triple-negative MDA-MB-468 breast cancer cell lineDalton Trans.51857–869(2022)DOI: 10.1039/d1dt03265h
For the development of anticancer drugs with higher activity and reduced
toxicity, two approaches were combined: preparation of platinum(IV) complexes exhibiting higher stability compared to their platinum(II)
counterparts and loading them into mesoporous silica SBA-15 with the
aim to utilise the passive enhanced permeability and retention (EPR)
effect of nanoparticles for accumulation in tumour tissues. Three
conjugates based on a cisplatin scaffold bearing the anti-inflammatory
drugs naproxen, ibuprofen or flurbiprofen in the axial positions (1, 2 and 3, respectively) were synthesised and loaded into SBA-15 to afford the mesoporous silica nanoparticles (MSNs) SBA-15|1, SBA-15|2 and SBA-15|3.
Superior antiproliferative activity of both free and immobilised
conjugates in a panel of four breast cancer cell lines (MDA-MB-468,
HCC1937, MCF-7 and BT-474) with markedly increased cytotoxicity with
respect to cisplatin was demonstrated. All compounds exhibit highest
activity against the triple-negative cell line MDA-MB-468, with
conjugate 1 being the most potent. However, against MCF-7 and BT-474 cell lines, the most notable improvement was found, with IC50
values up to 240-fold lower than cisplatin. Flow cytometry assays
clearly show that all compounds induce apoptotic cell death elevating
the levels of both early and late apoptotic cells. Furthermore,
autophagy as well as formation of reactive oxygen species (ROS) and
nitric oxide (NO) were elevated to a similar or greater extent than with
cisplatin.
Publikation
Bensing, C.; Mojić, M.; Gómez-Ruiz, S.; Carralero, S.; Dojčinović, B.; Maksimović-Ivanić, D.; Mijatović, S.; Kaluđerović, G. N.;Evaluation of functionalized mesoporous silica SBA-15 as a carrier system for Ph3Sn(CH2)3OH against the A2780 ovarian carcinoma cell lineDalton Trans.4518984-18993(2016)DOI: 10.1039/C6DT03519A
SBA-15|Sn3, a mesoporous silica-based material (derivative of SBA-15) loaded with an organotin compound Ph3Sn(CH2)3OH (Sn3), possesses improved antitumor potential against the A2780 high-grade serous ovarian carcinoma cell line in comparison to Sn3. It is demonstrated that both the compound and the nanostructured material are internalized by the A2780 cells. A similar mode of action of Sn3 and SBA-15|Sn3 against the A2780 cell line was found. Explicitly, induction of apoptosis, caspase 2, 3, 8 and 9 activation, accumulation of cells in the hypodiploid phase as well as accumulation of ROS were observed. Interestingly, Sn3 loaded in the mesoporous silica-based material needed to reach a concentration 3.5 times lower than the IC50 value of the Sn3 compound, pointing out a higher effect of the SBA-15|Sn3 than Sn3 alone. Clonogenic potential, growth in 3D culture as well as mobility of cells were disturbed in the presence of SBA-15|Sn3. Such behavior could be associated with the suppression of p-38 MAPK. Less profound effect of Sn3 compared to SBA-15|Sn3 could be attributed to a different regulation of p-38 and STAT-3, which are mainly responsible for an appropriate cellular response to diverse stimuli or metastatic properties.
Publikation
Barroso, S.; Coelho, A. M.; Gómez-Ruiz, S.; Calhorda, M. J.; Žižak, ?.; Kaluđerović, G. N.; Martins, A. M.;Correction: Synthesis, cytotoxic and hydrolytic studies of titanium complexes anchored by a tripodal diamine bis(phenolate) ligandDalton Trans.442497-2497(2015)DOI: 10.1039/C4DT90194K
Correction for ‘Synthesis, cytotoxic and hydrolytic studies of titanium complexes anchored by a tripodal diamine bis(phenolate) ligand’ by Sónia Barroso et al., Dalton Trans., 2014, 43, 17422–17433.